We propose to explore new non-linear photonic materials to enable time-of-flight (ToF) positron emission tomography (PET) detectors with <30 pico-second (ps) time resolution, as opposed to 500-900 picoseconds achieved by state-of-the-art PET systems that use scintillation crystals. PET is currently the standard-of-care for cancer management and an important tool in basic research. A PET system comprises a ring of position sensitive scintillation detectors. A PET scan collects millions of events comprising pairs of oppositely-directed 511 kilo-electron- volt (keV) photons that are emitted from the patient after injection of a radioactive contrast agent. The measured distribution of these two-photon hits recorded by the system detectors is used to reconstruct a 3-D image volume that represents the tracer biodistribution, which is used to characterize and quantify cellular and molecular disease states before and after treatment. If successful, the proposed <30 ps time resolution will enable an order of magnitude more accurate and precise localization of a positron decay event along the response line formed between any two 511 keV annihilation photon detector elements in a PET system. This disruptive technology would represent a tremendous paradigm shift for PET as it would drastically change the way a PET system operates. The fact that many more events would be accurately positioned along a response line through the patient enables substantial signal amplification for unprecedented ability to visualize and quantify disease signatures. The resulting huge image signal-to-noise (SNR) boost could also be exploited to reduce patient injected radioactive dose or scan time by a factor of 100, amazing features that would both continue to increase PET's widespread use as the standard-of-care for disease management, as well as open up new roles for the imaging modality in the clinic as well as in animal research into molecular mechanisms of disease. To achieve our goal of <30ps time resolution, we will explore non-linear photonic materials where picosecond changes in optical parameters are common and measured using modern optics methods, rather than using scintillation detectors which at best achieve hundreds of ps time resolution through spontaneous light emission processes and photodetection. The project will require the investigators to research and obtain several candidate high Z, high-density photonic materials; create an optical test bed for exploring fast temporal properties of photonic materials; measure ionization-induced modulation of optical properties in these materials; and investigate scaling up issues relevant to building a practical PET detector from these novel material and methods. This is an exciting multi-disciplinary project that involves concepts in fields such as physics, photonics, optics, electrical engineering, radiology, computer science, materials science, nano-science, and applied mathematics with a goal of enabling substantial improvements in ToF PET performance to drive important advances in the study and clinical management of cancer, cardiovascular disease and neurological disorders. The following contains confidential information that should not be used except for purpose of review and evaluation of this proposal.